The two isoenzymes for yeast NAD(+)-dependent glycerol 3-phosphate dehydrogenase encoded by GPD1 and GPD2 have distinct roles in osmoadaptation and redox regulation

The two isoenzymes for yeast NAD(+)-dependent glycerol 3-phosphate dehydrogenase encoded by GPD1 and GPD2 have distinct roles in osmoadaptation and redox regulation
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DOI:
10.1093/emboj/16.9.2179
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发表时间:
1997-05-01
期刊:
影响因子:
11.4
通讯作者:
Adler, L
Adler, L
中科院分区:
生物学1区
文献类型:
--
作者:
Ansell, R;Granath, K;Adler, L

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GPD1和GPD2两个同源基因编码酵母中依赖NAD的3-磷酸甘油脱氢酶同工酶,以前的研究表明GPD1的表达是由渗透胁迫诱导的,而GPD1 Delta突变体是渗透敏感的,因此GPD1具有完全不同的生理作用,GPD2的表达不受外界渗透浓度变化的影响,但受到缺氧条件的刺激,缺乏GPD2的突变株在厌氧条件下生长不良,GPD1和GPD2缺失的突变株不产生可检测到的甘油,高度敏感,在缺氧条件下不能生长,这种生长抑制伴随着细胞内NADH的强烈积累GPD2的厌氧诱导不受HOG途径的影响,HOG途径控制GPD1的渗透诱导,ROX1和ROX3也不影响GPD2的表达,ROX1和ROX3编码低氧和应激控制的基因表达。此外,在有氧条件下,添加亚硫酸氢盐诱导GPD2的表达,抑制乙醇发酵的最后还原步骤,从而导致NADH的积累,而乙醛的加入逆转了这种诱导。我们得出结论,GPD2的表达是由一种新的、不依赖于氧的信号通路控制的,这是在缺氧条件下调节代谢所必需的。
The two homologous genes GPD1 and GPD2 encode the isoenzymes of NAD-dependent glycerol 3-phosphate dehydrogenase in the yeast Saccharomyces cerevisiae, Previous studies showed that GPD1 plays a role in osmoadaptation since its expression is induced by osmotic stress and gpd1 Delta mutants are osmosensitive, Here we report that GPD2 has an entirely different physiological role, Expression of GPD2 is not affected by changes in external osmolarity, but is stimulated by anoxic conditions, Mutants lacking GPD2 show poor growth under anaerobic conditions, Mutants deleted for both GPD1 and GPD2 do not produce detectable glycerol, are highly osmosensitive and fail to grow under anoxic conditions, This growth inhibition, which is accompanied by a strong intracellular accumulation of NADH, is relieved by external addition of acetaldehyde, an effective oxidizer of NADH, Thus, glycerol formation is strictly required as a redox sink for excess cytosolic NADH during anaerobic metabolism, The anaerobic induction of GPD2 is independent of the HOG pathway which controls the osmotic induction of GPD1, Expression of GPD2 is also unaffected by ROX1 and ROX3, encoding putative regulators of hypoxic and stress-controlled gene expression. In addition, GPD2 is induced under aerobic conditions by the addition of bisulfite which causes NADH accumulation by inhibiting the final, reductive step in ethanol fermentation and this induction is reversed by addition of acetaldehyde, We conclude that expression of GPD2 is controlled by a novel, oxygen-independent, signalling pathway which is required to regulate metabolism under anoxic conditions.